Renoprotective effect of nifuroxazide in diabetes-induced nephropathy: impact on NFκB, oxidative stress, and apoptosis

Toxicol Mech Methods. 2018 Jul;28(6):467-473. doi: 10.1080/15376516.2018.1459995. Epub 2018 Apr 16.

Abstract

The prevalence of diabetes mellitus (DM) is drastically increased worldwide. Diabetic nephropathy (DN) is a microvascular complication of DM and a common cause of end stage renal disease (ESRD). DN has been recently reported as the most common cause among ESRD patients. Shortage of a definitive cure for DN and the social and economic burden of this disease provide considerable impetus for development of new therapies. In the present study, we evaluated the effect of nifuroxazide, a potent inhibitor of Janus kinase/signal transducers and activators of transcription (JAK2/STAT3), on nuclear factor kappa B (NFκB), oxidative stress, and apoptosis in diabetic kidney. Following induction of diabetes by single dose of streptozotocin (50 mg/kg), nifuroxazide was administrated to diabetic rats (25 mg/kg/day, orally) for 8 weeks. Our results showed that nifuroxazide treatment, attenuated diabetes-induced damage in renal structure, ameliorated oxidative stress, triggered antioxidant defense, reduced NFκB nuclear translocation and cleaved caspase-3 expression and down regulated the activity of apoptotic enzymes (caspase-3/caspase-8/caspase-9) in diabetic kidney. In conclusion, nifuroxazide exhibited renoprotective effect in diabetic kidney via dampening NFκB activation, oxidative stress, and apoptosis.

Keywords: Diabetic nephropathy; NFκB; apoptosis; nifuroxazide; oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Diabetes Mellitus, Experimental / complications*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / prevention & control*
  • Hydroxybenzoates / administration & dosage
  • Hydroxybenzoates / therapeutic use*
  • Janus Kinase 2 / antagonists & inhibitors
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • NF-kappa B / metabolism*
  • Nitrofurans / administration & dosage
  • Nitrofurans / therapeutic use*
  • Oxidative Stress / drug effects*
  • Rats, Sprague-Dawley
  • STAT3 Transcription Factor / antagonists & inhibitors
  • Signal Transduction

Substances

  • Hydroxybenzoates
  • NF-kappa B
  • Nitrofurans
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Jak2 protein, rat
  • Janus Kinase 2
  • nifuroxazide